Role of label-retaining cells in estrogen-induced endometrial regeneration

Reprod Sci. 2012 Jan;19(1):102-14. doi: 10.1177/1933719111414207. Epub 2011 Nov 7.


Candidate stem/progenitor cells have been identified in mouse endometrium as label-retaining cells (LRCs). The role of endometrial stem/progenitor cells in initiating estrogen-stimulated endometrial growth in prepubertal and cycling mice was investigated following a single 17β-estradiol (E2) injection in bromodeoxyuridine (BrdU)-labeled and -chased (LRC), ovariectomised mice. Proliferating (BrdU(+)/Ki-67(+)) and mitotic (BrdU(+)/PH3(+)) epithelial LRCs were first detected in prepubertal mice 8 hours following E2 treatment, initiating the proliferative response. In contrast, all epithelial LRCs and 16% of epithelial cells in cycling mice proliferated within 2 hours. In cycling mice, 12% of stromal LRCs initiated a proliferative response 8 hours after E2. Proliferating epithelial LRCs and most stromal LRCs (85%) lacked estrogen receptor-α (ESR1). These findings suggest that endometrial epithelial LRCs function as stem/progenitor cells by receiving proliferative signals from neighboring ESR1(+) niche cells to initiate the growth of the epithelium during development, while mature epithelial cells may undergo self-replication in cycling endometrium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Endometrium / cytology*
  • Endometrium / drug effects*
  • Estrogens / pharmacology*
  • Female
  • Mice
  • Random Allocation
  • Regeneration / drug effects*
  • Stem Cells / drug effects*


  • Estrogens